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Evaluation of Porcine Pancreatic Islets Transplanted in the Kidney Capsules of Diabetic Mice Using a Clinically Approved Superparamagnetic Iron Oxide (SPIO) and a 1.5T MR Scanner

  • Kim, Hoe-Suk (Department of Radiology, Seoul National University Hospital) ;
  • Kim, Hyoung-Su (Department of Radiology, Seoul National University Hospital) ;
  • Park, Kyong-Soo (Department of Internal Medicine, Seoul National University Hospital) ;
  • Moon, Woo-Kyung (Department of Radiology, Seoul National University Hospital)
  • 투고 : 2009.12.01
  • 심사 : 2010.07.22
  • 발행 : 2010.12.01

초록

Objective: To evaluate transplanted porcine pancreatic islets in the kidney capsules of diabetic mice using a clinically approved superparamagnetic iron oxide (SPIO) and a 1.5T MR scanner. Materials and Methods: Various numbers of porcine pancreatic islets labeled with Resovist, a carboxydextran-coated SPIO, were transplanted into the kidney capsules of normal mice and imaged with a 3D FIESTA sequence using a 1.5T clinical MR scanner. Labeled (n = 3) and unlabeled (n = 2) islets were transplanted into the kidney capsules of streptozotocin-induced diabetic mice. Blood glucose levels and MR signal intensities were monitored for 30 days post-transplantation. Results: There were no significant differences in viability or insulin secretion between labeled and unlabeled islets. A strong correlation ($r^2$ > 0.94) was evident between the number of transplanted islets and $T_2$ relaxation times quantified by MRI. Transplantation with labeled or unlabeled islets helped restore normal sustained glucose levels in diabetic mice, and nephrectomies induced the recurrence of diabetes. The MR signal intensity of labeled pancreatic islets decreased by 80% over 30 days. Conclusion: The transplantation of SPIO-labeled porcine islets into the kidney capsule of diabetic mice allows to restore normal glucose levels, and these islets can be visualized and quantified using a 1.5T clinical MR scanner.

키워드

과제정보

연구 과제 주관 기관 : NRF

참고문헌

  1. Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000;343:230-238 https://doi.org/10.1056/NEJM200007273430401
  2. Shapiro AM, Ricordi C, Hering B. Edmonton's islet success has indeed been replicated elsewhere. Lancet 2003;362:1242
  3. Kim SJ, Doudet DJ, Studenov AR, Nian C, Ruth TJ, Gambhir SS, et al. Quantitative micro positron emission tomography (PET) imaging for the in vivo determination of pancreatic islet graft survival. Nat Med 2006;12:1423-1428
  4. Evgenov NV, Medarova Z, Dai G, Bonner-Weir S, Moore A. In vivo imaging of islet transplantation. Nat Med 2006;12:144-148 https://doi.org/10.1038/nm1316
  5. Elliott RB, Escobar L, Tan PL, Garkavenko O, Calafiore R, Basta P, et al. Intraperitoneal alginate-encapsulated neonatal porcine islets in a placebo-controlled study with 16 diabetic cynomolgus primates. Transplant Proc 2005;37:3505-3508 https://doi.org/10.1016/j.transproceed.2005.09.038
  6. Cozzi E, Bosio E. Islet xenotransplantation: current status of preclinical studies in the pig-to-nonhuman primate model. Curr Opin Organ Transplant 2008;13:155-158 https://doi.org/10.1097/MOT.0b013e3282f97842
  7. Moore A, Marecos E, Bogdanov A Jr, Weissleder R. Tumoral distribution of long-circulating dextran-coated iron oxide nanoparticles in a rodent model. Radiology 2000;214:568-574
  8. Lewin M, Carlesso N, Tung CH, Tang XW, Cory D, Scadden DT, et al. Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat Biotechnol 2000;18:410-414 https://doi.org/10.1038/74464
  9. Bulte JW, Zhang S, van Gelderen P, Herynek V, Jordan EK, Duncan ID, et al. Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. Proc Natl Acad Sci U S A 1999;96:15256-15261 https://doi.org/10.1073/pnas.96.26.15256
  10. Dodd CH, Hsu HC, Chu WJ, Yang P, Zhang HG, Mountz JD Jr, et al. Normal T-cell response and in vivo magnetic resonance imaging of T-cells loaded with HIV transactivator-peptidederived superparamagnetic nanoparticles. J Immunol Methods 2001;256:89-105 https://doi.org/10.1016/S0022-1759(01)00433-1
  11. Dousset V, Delalande C, Ballarino L, Quesson B, Seilhan D, Coussemacq M, et al. In vivo macrophage activity imaging in the central nervous system detected by magnetic resonance. Magn Reson Med 1999;41:329-333 https://doi.org/10.1002/(SICI)1522-2594(199902)41:2<329::AID-MRM17>3.0.CO;2-Z
  12. Jung SI, Kim SH, Kim HC, Son KR, Chung SY, Moon WK, et al. In vivo MR imaging of magnetically labeled mesenchymal stem cells in a rat model of renal ischemia. Korean J Radiol 2009;10:277-284 https://doi.org/10.3348/kjr.2009.10.3.277
  13. Jirak D, Kriz J, Herynek V, Andersson B, Girman P, Burian M, et al. MRI of transplanted pancreatic islets. Magn Reson Med 2004;52:1228-1233 https://doi.org/10.1002/mrm.20282
  14. Shapiro AM, Hao EG, Lakey JR, Yakimets WJ, Churchill TA, Mitlianga PG, et al. Novel approaches toward early diagnosis of islet allograft rejection. Transplantation 2001;71:1709-1718 https://doi.org/10.1097/00007890-200106270-00002
  15. Evgenov NV, Medarova Z, Pratt J, Pantazopoulos P, Leyting S, Bonner-Weir S, et al. In vivo imaging of immune rejection in transplanted pancreatic islets. Diabetes 2006;55:2419-2428 https://doi.org/10.2337/db06-0484
  16. Tai JH, Foster P, Rosales A, Feng B, Hasilo C, Martinez V, et al. Imaging islets labeled with magnetic nanoparticles at 1.5 Tesla. Diabetes 2006;55:2931-2938 https://doi.org/10.2337/db06-0393
  17. Symonds P, Murray JC, Hunter AC, Debska G, Szewczyk A, Moghimi SM. Low and high molecular weight poly(L-lysine)s/ poly(L-lysine)-DNA complexes initiate mitochondrial-mediated apoptosis differently. FEBS Lett 2005;579:6191-6198 https://doi.org/10.1016/j.febslet.2005.09.092
  18. Kim HS, Choi Y, Song IC, Moon WK. Magnetic resonance imaging and biological properties of pancreatic islets labeled with iron oxide nanoparticles. NMR Biomed 2009;22:852-856 https://doi.org/10.1002/nbm.1398
  19. Matuszewski L, Persigehl T, Wall A, Schwindt W, Tombach B, Fobker M, et al. Cell tagging with clinically approved iron oxides: feasibility and effect of lipofection, particle size, and surface coating on labeling efficiency. Radiology 2005;235:155- 161 https://doi.org/10.1148/radiol.2351040094
  20. Kim JH, Kim HI, Lee KW, Yu JE, Kim SH, Park HS, et al. Influence of strain and age differences on the yields of porcine islet isolation: extremely high islet yields from SPF CMS miniature pigs. Xenotransplantation 2007;14:60-66 https://doi.org/10.1111/j.1399-3089.2006.00364.x
  21. van der Burg MP, Basir I, Bouwman E. No porcine islet loss during density gradient purification in a novel iodixanol in University of Wisconsin solution. Transplant Proc 1998;30:362- 363 https://doi.org/10.1016/S0041-1345(97)01308-0
  22. Reimer P, Balzer T. Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: properties, clinical development, and applications. Eur Radiol 2003;13:1266-1276
  23. Berkova Z, Kriz J, Girman P, Zacharovova K, Koblas T, Dovolilova E, et al. Vitality of pancreatic islets labeled for magnetic resonance imaging with iron particles. Transplant Proc 2005;37:3496-3498 https://doi.org/10.1016/j.transproceed.2005.09.052
  24. Evgenov NV, Pratt J, Pantazopoulos P, Moore A. Effects of glucose toxicity and islet purity on in vivo magnetic resonance imaging of transplanted pancreatic islets. Transplantation 2008;85:1091-1098 https://doi.org/10.1097/TP.0b013e31816b183e
  25. Jirak D, Kriz J, Strzelecki M, Yang J, Hasilo C, White DJ, et al. Monitoring the survival of islet transplants by MRI using a novel technique for their automated detection and quantification. MAGMA 2009;22:257-265 https://doi.org/10.1007/s10334-009-0172-4
  26. Kriz J, Jira′k D, Girman P, Berkova′Z, Zacharovova K, Honsova E, et al. Magnetic resonance imaging of pancreatic islets in tolerance and rejection. Transplantation 2005;80:1596-1603 https://doi.org/10.1097/01.tp.0000183959.73681.b9

피인용 문헌

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  2. Magnetic separation of encapsulated islet cells labeled with superparamagnetic iron oxide nano particles vol.20, pp.4, 2013, https://doi.org/10.1111/xen.12042
  3. Imaging of transplanted islets by positron emission tomography, magnetic resonance imaging, and ultrasonography vol.5, pp.5, 2013, https://doi.org/10.4161/isl.26980
  4. Insulin-producing cells from embryonic stem cells rescues hyperglycemia via intra-spleen migration vol.4, pp.None, 2010, https://doi.org/10.1038/srep07586
  5. Transplantation of human mobilized mononuclear cells improved diabetic neuropathy vol.239, pp.3, 2010, https://doi.org/10.1530/joe-18-0516
  6. Transplantation of human mobilized mononuclear cells improved diabetic neuropathy vol.239, pp.3, 2010, https://doi.org/10.1530/joe-18-0516